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Effects of pentoxifylline and tocopherol on an osteoradionecrosis animal model
Affiliation:1. Department of Oral and Maxillofacial Surgery, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, South Korea;2. Department of Dental Biomaterials Science, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, South Korea;3. Dental Pharmacology & Dental Therapeutics, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, South Korea;4. Department of Oral Pathology, College of Dentistry, Gangneung-Wonju National University, Gangneung, South Korea;1. Center for Cleft Lip and Palate Treatment, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Ba-da-chu, Beijing 100144, China;2. Digital Simulation Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Ba-da-chu, Beijing 100144, China;3. Research Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Ba-da-chu, Beijing 100144, China;1. Department of Oto-Rhino-Laryngology, University Hospitals Leuven, Leuven, Belgium;2. Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium;1. Department of Biomedical Radiation Sciences (Head: Sung-Joon Ye, PhD), Graduate School of Convergence Science and Technology, Seoul National University, South Korea;2. Orthognathic Surgery Center (Head: Soon Jung Hwang, DDS, MD, PhD), Seoul National University Dental Hospital, South Korea;3. Department of Oral and Maxillofacial Radiology (Head: Min-Suk Heo, DDS, PhD), School of Dentistry and Dental Research Institute, Seoul National University, South Korea;4. Department of Oral and Maxillofacial Surgery (Head: Jin-Young Choi, DDS, MD, PhD), School of Dentistry, Dental Research Institute, BK21 Plus, Seoul National University, South Korea;1. Department of Oral and Maxillofacial Surgery (Head: Prof. Jin Young Choi), Dental Research Institute, School of Dentistry, Seoul National University, Seoul, South Korea;2. Department of Dental Hygiene (Head: Prof. Yeon Sook Kim), Cheongju University, Cheongju, South Korea;3. Department of Oral Pathology (Head: Prof. Suk Keun Lee), College of Dentistry, Gangneung-Wonju National University, 123 Chibyun-dong, Gangneung 210-702, South Korea;1. Department of Internal Medicine, Saint Vincent Hospital, Worcester, Massachusetts, USA;2. Division of Infectious Diseases, Saint Vincent Hospital and Reliant Medical Group, Worcester, Massachusetts, USA;1. Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Seoul National University, Seoul, Republic of Korea;2. Oral Oncology Clinic, Research Institute & Hospital, National Cancer Centre, Goyang, Republic of Korea;3. Department of Oral and Maxillofacial Surgery, Korea University Guro Hospital, Seoul, Republic of Korea;4. Department of Occupation and Environment, Konkuk Postgraduate Medical School, Choong-Ju, Republic of Korea;5. Department of Oral and Maxillofacial Surgery, Hepsiba Clinic, Seoul, Republic of Korea
Abstract:PurposeOsteoradionecrosis (ORN) is known to be a refractory disease in the oral and maxillofacial field. The purpose of this study was to examine the effects of pentoxifylline (PTX) and tocopherol (TP) on an ORN animal model focused on bone healing.Materials and methodsA total of 48 Sprague–Dawley rats were used: 40 received a single irradiation dose of 35 Gy on the left mandible, and eight were used as the nonirradiated control group. The rats received PTX (T1, C1), TP (T2, C2), a combination of PTX and TP (T3, C3), or normal saline (T4, C4). Three weeks after irradiation, the mandibular posterior teeth were extracted. The rats were sacrificed 4 weeks after extraction.ResultsIn the T3 group, bone volume/tissue volume was 19.62 ± 16.03 (%), bone mineral density was as 0.31 ± 0.16 (g/cm3) in the micro-CT analysis, which were higher than that of other groups (p = 0.025, p = 0.012, respectively). In the histological analysis, bone regeneration was the most prominent in the T3 group. The ratio of empty lacunae was the highest in the T4 group, 68.77 ± 15.47 (%, p = 0.004). Immunohistochemistry showed that the expression of TNF-α was relatively lower in the T3 than in the T4 or T2 groups. The RT-qPCR showed the expression level of PECAM, VEGF-A, and osteocalcin was more than twofold as high as in the T3 group compared to the other groups.ConclusionThe combination of PTX and TP appears to promote angiogenesis and osteogenesis in a rat ORN model. Therefore, PTX and TP might be useful in the treatment and prevention of ORN.
Keywords:Osteoradionecrosis (ORN)  Pentoxifylline (PTX)  Tocopherol (TP)
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